Transurethral systems and methods for ablation treatment of prostate tissue

ABSTRACT

Transurethral systems and methods for delivering electrical energy and controlled, mild heating to a prostate tissue of a patient for destruction of cancerous and/or hyperplastic tissue. A method includes positioning an elongate urethral probe having an expandable member with electrode elements at a target location in the patient&#39;s urethra, and inflating or expanding at the target location. Secondary electrodes are positioned within or adjacent to the prostate tissue and spaced from the electrode elements of the expandable member, and an alternating electrical current flow is established between the electrode elements of the expandable member and the one or more secondary electrodes. Current delivery can be selected so as to destroy or ablate cancerous cells of the prostate tissue.

CROSS-REFERENCE

This application is a divisional application of U.S. patent applicationSer. No. 12/283,940, filed Sep. 15, 2008, which claims the benefit ofU.S. Provisional Patent Application No. 60/972,698, filed Sep. 14, 2007,the contents of each of which are incorporated herein by reference.

BACKGROUND OF THE INVENTION

The present invention relates generally to electric field delivery to aprostate tissue of a patient. More particularly, the present inventionprovides transurethral systems and methods for delivering electricalenergy and controlled, mild heating to a prostate tissue of a patientfor destruction of cancerous and/or hyperplastic tissue.

The prostate gland is a walnut-sized gland located in the pelvic area,just below the outlet of the bladder and in front of the rectum. Itencircles the upper part of the urethra, which is the tube that emptiesurine from the bladder. The prostate is an important part of the malereproductive system, requiring male hormones like testosterone tofunction properly, and helps to regulate bladder control and normalsexual functioning. The main function of the prostate gland is to storeand produce seminal fluid, a milky liquid that provides nourishment tosperm, and increases sperm survival and mobility.

Cancer of the prostate is characterized by the formation of malignant(cancerous) cells in the prostate. Prostate cancer is the leading cancerrelated cause of death in men in the United States. There are currentlyover 2 million men in the United States with prostate cancer, and it isexpected that there will be approximately 190,000 new cases of prostatecancer diagnosed, with 28,000 men dying from the disease in 2008.

In addition to risks of morbidity due to prostate cancer, most men over60 years old experience partial or complete urinary obstruction due toenlargement of the prostate. This condition can originate from prostatecancer, or more typically, from benign prostatic hyperplasia (BPH),which is characterized by an increase in prostate size and tissue massnear the urethra.

Common active treatment options include surgery and radiation. Surgeryoften includes the complete surgical removal of the prostate gland(“Radical Prostatectomy”), and in certain instances the regional lymphnodes, in order to remove the diseased tissue from the body. In someinstances, a nerve sparing prostatectomy is attempted in an effort tomaintain erectile function in the patient after treatment. Side effectsassociated with radical prostatectomy can include pain, inflammation,infection, incontinence, shorter penis and impotence.

Radiation therapy is another treatment option for prostate cancer and ischaracterized by the application of ionizing radiation to the diseasedarea of the prostate. Ionizing radiation has the effect of damaging acells DNA and limiting its ability to reproduce. For Prostate Cancertreatment, two methods of radiation therapy include External BeamRadiation Therapy (EBRT) and internal radiation, commonly known asBrachytherapy. EBRT involves the use of high-powered X-rays deliveredfrom outside the body. The procedure is painless and only takes a fewminutes per treatment session, but needs to be done extended periods offive days a week, for about seven or eight weeks. During EBRT, the rayspass through and can damage other tissue on the way to the tumor,causing side effects such as short-term bowel or bladder problems, andlong-term erectile dysfunction. Radiation therapy can also temporarilydecrease energy levels and cause loss of appetite.

Brachytherapy involves the injection of tiny radioactive isotopecontaining ‘seeds’ into the prostate. Once positioned in the tissue, theradiation from the seeds extends a few millimeters to deliver a higherradiation dose in a smaller area, causing non-specific damage to thesurrounding tissue. The seeds are left in place permanently, and usuallylose their radioactivity within a year. Internal radiation also causesside effects such as short-term bowel or bladder problems, and long-termerectile dysfunction. Internal radiation therapy can also temporarilydecrease energy levels and cause loss of appetite. It is also common forthe implanted seeds to migrate from the prostate into the bladder andthen be expelled through the urethra during urination. Most significant,however, is the change in the texture of the prostate tissue over time,making the subsequent removal of the gland, as described above,complicated and difficult as a secondary treatment.

Given the significant side-effects with existing treatments such asradical prostatectomy and radiation therapy, less invasive and lesstraumatic systems and procedures have been of great interest. One suchmore minimally invasive system developed in recent years includes socalled “Trans-urethral Needle Ablation” or TUNA, which involves passinga radio-frequency (RF) device such as a catheter probe or scope into theurethra for delivery of high frequency energy to the tissue. The RFinstruments include electrode tips that are pushed out from the side ofthe instrument body along off-axis paths to pierce the urethral wall andpass into the prostatic tissue outside of the urethra. High-frequencyenergy is then delivered to cause high-temperature ionic agitation andfrictional heating to tissues surrounding the electrodes. Thehigh-temperature induced in the tissue includes induction of extremelyhigh temperatures, often up 100 degrees C., and is generally isnon-specific to cancerous tissue, destroying both healthy andnon-healthy tissue.

Another technique developed in recent years for treating BPH isTrans-urethral Microwave Thermo Therapy (or “TUMT”). This techniqueinvolves use of a device having a microwave probe or antenna locatednear its distal end and connected to an external generator of microwavepower outside the patient's body. The microwave probe is inserted intothe urethra to the point of the prostate for energy delivery andmicrowave electromagnetic heating. Since the microwave probe deliverssubstantial heating that can cause unwanted damage to healthy tissues orto the urethra, devices typically make use of a cooled catheter toreduce heating immediately adjacent to the probe. The objective is tocarefully balance cooling of the urethra to prevent damage to it by theheating process, while at the same time delivering high temperatureheating (greater than 50 degrees C.) to the prostatic tissue outside ofand at a distance from the urethra. In this procedure, the prostatictissue immediately around the urethra and the urethra itself aredeliberately spared from receiving an ablative level of heating byattempting to keep the temperatures for these structures at less than 50degrees C. Unfortunately, controlling the tissue heating due to theapplied microwave energy is difficult and unintended tissue damage canoccur. Further, destruction of tissue beyond the cooled region isindiscriminate, and control of the treatment zone is imprecise andlimited in the volume of tissue that can be effectively treated.

Accordingly, there is a continuing interest to develop less invasivedevices and methods for the treatment of BPH and prostate cancer that ismore preferential to destruction of target tissue and more preciselycontrollable.

SUMMARY OF THE INVENTION

The present invention includes methods and systems for applying electricfields to prostate tissue of a patient for controllable and/orpreferential cancerous cell destruction and tissue ablation. Methods andsystems according to the present invention will typically include useand positioning of an elongate urethral probe that can be inserted inthe urethra of the patient and advanced along the patient's urethra forpositioning at a desired location. A urethral probe includes a distallypositioned expandable member, such as a balloon configured for expansionin the urethra of the patient. The probe can be coupled to a controlleror control unit and power source, such as coupled about a proximalportion positioned externally to the patient's body during treatment.The expandable member will include conductive electrode elementspatterned or disposed on an outer surface of the expandable member. Theelongated body or shaft of the probe can include an inner lumen orpassage with electrical coupling members, such as insulated wires, forcoupling the electrode elements of the expandable member to the proximalend and/or an externally positioned controller and/or power source. Thedistal portion of the urethral probe is insertable in the urethra andcan be advanced through the patient's urethra so as to position theexpandable member at a target location in the patient's urethra,including a portion or length of the urethra passing through thepatient's prostate. Upon locating the distal portion at the targetlocation, the balloon or expandable member can be inflated or expandedso as to position or bring the conductive electrode elements in improvedor better contact with an inner surface of the patient's urethra at thetarget location, for energy delivery and establishing current flow inthe desired manner. The electrode elements can be positioned such thatapplied electric fields extend or radiate throughout the target tissueregion. In some embodiments, energy is applied to deliver mild andcontrolled heating of the tissue.

As described above, electrode elements of the expandable member of theurethral probe can be electrically coupled to a control unit and/orpower source for energy delivery and establishment of the desiredelectric field through the target tissue or a volume of the prostatetissue to be treated. Energy delivery can include establishing anelectrical current flow between the electrode elements of the expandablemember and the one or more secondary electrodes positioned within oradjacent to the prostate tissue and spaced from the electrode elementsof the expandable member. Current flow is established between electrodeelements of the expandable member and the secondary electrodes in abipolar arrangement for formation of a sort of current circuit, allowingthe applied field to substantially be contained between the electrodesor within the volume defined by the secondary electrodes with theexpandable member positioned in the defined volume. Thus, the controlunit and power source can be coupled to the urethral probe and electrodeelements of the expandable member, and configured for energy applicationand establishment of current flow through the target tissue region,including a volume of the patient's prostate tissue substantiallydefined by the positioned electrodes/electrode elements.

The control system and power source can be configured for delivery ofvarious possible energy ranges including, e.g., alternating electricalcurrent flow in the radiofrequency (RF) range. Energy applicationaccording to the present invention can be selected to establish analternating electrical current flow through the tissue sufficient tomildly heat or deliver low levels of hyperthermia. Thus, current flowcan be delivered to generate small changes/elevations in temperature inthe target tissue region, with resulting hyperthermic effects typicallycausing average tissue temperatures of less than about 50 degrees C.,and typically about 40-48 degrees C. (e.g., about 42-45 degrees C.). Inone example, energy delivery will include relatively low power ablationincluding intermediate current frequency less than about 300 kHz, andtypically about 50 kHz to about 250 kHz. Further, energy delivery, incertain embodiments, can include establishing current flow fieldssubstantially radially throughout the target tissue and/or in aplurality of different directions. For example, energy delivery caninclude creating a current flow field extending radially from the anelectrode or electrode elements positioned within a treatment volume,such as the electrode elements of the urethral probe expandable memberpositioned in the urethra of the patient. Energy delivery in the mannerdescribed herein provides numerous advantages, including preciselycontrolling the energy application to the target tissue, controllingthermal effects in the desired heating ranges (e.g., mild hyperthermia),and preferentially destroying cancerous cells with limited or noobservable damage to healthy or non-cancerous tissues.

Thus, in one aspect, the present invention includes methods and systemsfor delivering an electric field to ablate or destroy cancerous cells ofa prostate tissue of a patient including positioning of an elongateurethral probe comprising a proximal end and a distal portion having anexpandable member, and one or more conductive electrode elementsdisposed on an outer surface of the expandable member. Electric fielddelivery includes advancing the distal portion of the probe through thepatient's urethra so as to position the expandable member at a targetlocation in the patient's urethra. Once positioned, the expandablemember is inflated or expanded at the target location so as to positionthe conductive electrode elements in contact with an inner surface ofthe patient's urethra at the target location. One or more secondaryelectrodes are positioned within or adjacent to the prostate tissue andspaced from the electrode elements of the expandable member, and analternating electrical current flow is established between the electrodeelements of the expandable member and the one or more secondaryelectrodes. Current delivery can be selected so as to preferentiallydestroy cancerous cells of the prostate tissue.

In another aspect, systems and methods include an elongate urethralprobe including a proximal end and a distal portion having an expandablemember, and one or more conductive electrode elements disposed on anouter surface of the expandable member. The probe further includes oneor more secondary electrodes deployable from a body of the elongateprobe. A method includes advancing the distal portion of the probethrough the patient's urethra so as to position the expandable member ata target location in the patient's urethra. The positioned expandablemember is inflated or expanded at the target location so as to positionthe conductive electrode elements in contact with an inner surface ofthe patient's urethra at the target location. The deployable electrodescan be advanced or deployed from the body of the probe and through theurethral wall into the prostate tissue and spaced from the positionedexpandable member. The deployed electrodes advanced or positioned inthis manner can be positioned to substantially define an ablation volumewith the expandable member positioned within the ablation volume. Themethod further includes establishing an electrical current flow betweenthe electrode elements of the expandable member and the one or moresecondary electrodes.

In yet another aspect, methods and systems of the present inventioninclude an elongate urethral probe one or more individual elongatedneedle electrodes that can be separately, from the urethral probe,positioned in the prostate tissue or the vicinity of the prostatetissue. Elongated needle electrodes will include a distal portion thatcan include a sharpened distal tip and a proximal portion. A method caninclude advancing the distal portion of the probe through the patient'surethra so as to position the expandable member at a target location inthe patient's urethra, and expanding the expandable member at the targetlocation so as to position the conductive electrode elements in contactwith an inner surface of the patient's urethra at the target location.The method further includes positioning the elongated needle electrodeswithin or adjacent to the prostate tissue and spaced from the electrodeelements of the expandable member. The positioning can be accomplishedby advancing the needle electrodes through the perineum of the patientand into the prostate tissue in the desired location. Once the urethralprobe and needle electrodes are positioned, treatment includesestablishing an electrical current flow between the electrode elementsof the expandable member and the positioned needle electrodes.

In another aspect of the present invention, methods and systems includean elongate urethral probe having a plurality of deployable electrodesthat can be advanced through the urethral wall and into the prostatetissue in a desired arrangement for energy delivery. An elongateurethral probe can include a proximal end, a distal portion, and aplurality of electrodes deployable from the distal portion. A method caninclude advancing the distal portion of the probe through the patient'surethra so as to position the distal portion near a target location inthe patient's urethra. Once the distal portion is at the desiredlocation, a plurality of outer or secondary electrodes can be deployedfrom the distal portion of the probe, through the urethral wall, andinto the prostate tissue. The deployed outer or secondary electrodes canbe positioned to substantially define an ablation volume in the prostatetissue. Further, an inner or central electrode can be deployed from thedistal portion of the probe and through the urethral wall and into theprostate tissue such that the inner/central electrode is positionedwithin the ablation volume. Once the urethral probe and needleelectrodes are positioned, treatment includes establishing an electricalcurrent flow between the inner electrode and the one or moreouter/secondary electrodes.

In yet another aspect, the present invention includes various systemsfor delivery of energy for treatment according to the methods of thepresent invention, including establishing electrical current flow forpreferential destruction of cancerous or hyperplastic cells of aprostate tissue of a patient. In one embodiment, a system includes anelongate urethral probe comprising a proximal end and a distal portionhaving an expandable member, the expandable member including one or moreconductive electrode elements. The system further includes a rectalprobe having one or more electrode elements disposed on a surface of anexpandable member. A control system including a power source is furtherincluded, the control system can be coupled to the elongate urethralprobe and rectal probe and configured to provide alternating electricalcurrent to the electrodes so as to establish a current flow through avolume of the patient's prostate tissue and between the electrodeelements of the urethral probe and electrode elements of the rectalprobe.

In yet another embodiment, the present invention includes methods andsystems for delivering an electric field to destroy cancerous orproliferating cells of a target tissue or of a body lumen passingthrough a target tissue of a patient. Systems and methods includepositioning of an elongate probe in a body lumen of the patient, theprobe including a proximal end and a distal portion having an expandablemember, and one or more conductive electrode elements disposed on anouter surface of the expandable member. The distal portion of the probecan be advanced through the patient's body lumen so as to position theexpandable member at a target location in the lumen. Once positioned,the expandable member can be expanded (e.g., inflated, deployed) at thetarget location so as to position the conductive electrode elements intocontact (e.g., improved or better contact) with an inner surface of thepatient's lumen. Systems and methods further include positioning one ormore secondary electrodes within or adjacent to the target tissue andspaced from the electrode elements of the expandable member, andestablishing an electrical current flow between the electrode elementsof the expandable member and the one or more secondary electrodes.Current flow may be selected so as to preferentially destroy cancerouscells of the target tissue, and may include application of mild tissueheating or hyperthermia. A body lumen can include any cavity ortube-like body organ or passage in a patient's body.

For a fuller understanding of the nature and advantages of the presentinvention, reference should be made to the ensuing detailed descriptionand accompanying drawings. Other aspects, objects and advantages of theinvention will be apparent from the drawings and detailed descriptionthat follows.

INCORPORATION BY REFERENCE

All publications, patents, and patent applications mentioned in thisspecification are herein incorporated by reference to the same extent asif each individual publication, patent, or patent application wasspecifically and individually indicated to be incorporated by reference.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the invention are set forth with particularity inthe appended claims. A better understanding of the features andadvantages of the present invention will be obtained by reference to thefollowing detailed description that sets forth illustrative embodiments,in which the principles of the invention are utilized, and theaccompanying drawings of which:

FIG. 1 illustrates a transurethral system and imaging system accordingto an embodiment of the present invention.

FIG. 2 illustrates a system including transurethral ablation probecoupled with a power supply and control unit, according to an embodimentof the present invention.

FIGS. 3A and 3B illustrate elongate transurethral probes according tovarious embodiments of the present invention.

FIGS. 4A through 4C illustrate current field delivery in a target tissueaccording to various embodiments of the present invention.

FIGS. 5A and 5B respectively illustrate a system including atransurethral probe and elongate needle electrodes, and electrodepositioning in such a system, according to an embodiment of the presentinvention.

FIGS. 6A through 6C illustrate exemplary electrode embodiments,according to the present invention.

FIGS. 7A through 7C illustrate a transurethral probe having deployablesecondary electrodes and probe positioning in the prostate tissue of apatient, according to an embodiment of the present invention.

FIGS. 8A and 8B illustrate current delivery in the prostate tissue of apatient between a transurethral probe and rectal probe, according to anembodiment of the present invention.

FIG. 9 illustrates a transurethral probe having a distal positioningballoon, according to an embodiment of the present invention.

FIGS. 10A through 10D illustrates a urethral probe having deployableelectrodes that can be advanced through the urethral wall and into theprostate tissue of a patient. FIG. 10B illustrates current flow betweenpositioned electrodes, according to an embodiment of the presentinvention.

FIG. 11 includes a diagram illustrating a system according to anembodiment of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

The present invention includes systems and methods for more preciselycontrolled energy deliver to prostate tissue for applying fields,including controlled delivery and generation of mild heating orhyperthermia to prostate tissue for the destruction of cancerous and/ortreatment of hyperplastic prostate cells for treatment of benignprostatic hyperplasia (BPH).

The systems and methods described herein generally utilize an elongateurethral probe that can be inserted in the urethra of the patient andadvanced along the patient's urethra for positioning at a desiredlocation. A urethral probe can include distal expandable member orballoon configured for expansion in the urethra of the patient. Theexpandable member includes conductive electrode elements patterned ordisposed on an outer surface of the expandable member. The distalportion of the urethral probe is inserted into the urethra and advancedto position the expandable member at a target location in the patient'surethra, and the expandable member inflated or expanded so as to bringthe conductive electrode elements into improved contact with theurethral wall. Energy delivery and desired tissue heating isaccomplished by establishing electrical current flow between electrodesof the expandable member and one or more electrodes (e.g., secondaryelectrodes) positioned in or in the vicinity of the prostate tissue andspaced from the urethral probe expandable member.

Establishment and application of energy delivery utilizing the describedenergy parameters and/or field delivery (e.g., orientation) can offerseveral advantages. First, energy delivery according to the presentinvention further advantageously allows a more controlled or precisetherapeutic energy dose both in terms of delivery of the desired currentand resulting effects, as well as more accurate delivery to the targetor intended tissue. For example, current flow is established betweenelectrodes in a bipolar arrangement, with current flow established andsubstantially contained between the spaced electrodes. Further, tissueheating can be more precisely controlled to prevent or minimizeexcessive heating and/or hot spots that can cause unintended damage tohealthy or non-target tissues. For example, energy delivery can beselected (e.g., frequency ranges between about 50 kHz to about 300 kHz)such that tissue heating occurs significantly, and in some casespredominately, due to tissue resistance, rather than the high-frictionalheating observed at high frequencies (e.g., 500 kHz or greater), thelatter of which can include significant tissue temperature gradientsthroughout the treated tissue, with significant tissue temperaturechanges occurring through a volume of treated tissue as a function ofelectrode distance. While heating may occur due to both tissueresistance and frictional heating, with relative reduction of highfriction type heating a more constant and controlled heating betweenopposing electrodes may be delivered.

Another advantage of the present inventive methods and systems is thatenergy delivery and application of mild hyperthermia as described hasbeen observed to be surprisingly effective in preferentially damagingand destroying cancerous cells compared to non-cancerous or healthycells/tissue. Preferential destruction, as described herein, refers toestablishing current flow as described with application of hyperthermia,generally below about 50 degrees C., such that cytotoxic effects oftreatment are, on average or as a whole, more destructive and/or lethalto cancerous or hyperplastic cells (e.g., cells exhibiting orpredisposed to exhibiting unregulated growth) compared to non-cancerousor healthy cells. In some instances, establishing current flow andinduction of mild hyperthermia as described herein is remarkablyeffective in preferentially destroying cancerous cells with limited orno observable damage to non-cancerous tissues.

Furthermore, and without being bound by any particular theory, electrodeconfiguration and field application as described in certain embodiments(e.g., radially and/or in a plurality of different directions) may takeadvantage of tumor or mitotic cell physiology to increase treatmenteffectiveness, and can include a more optimal or effective orientationof the applied field with respect to dividing cells of the targetregion. For example, energy application can be accomplished such thatcurrent fields are substantially aligned at some point during energydelivery with division axes of dividing cells (e.g., cancerous cells),thereby more effectively disrupting cellular processes or mitotic events(e.g., mitotic spindle formation and the like). As cancerous cells aredividing at a higher rate compared to non-cancerous cells, fieldapplication in this manner may preferentially damage cancerous cellscompared to healthy or non-dividing cells. It will be recognized,however, that energy application according to the present inventionlikely has several or numerous cytotoxic effects on cells of the targetregion and that such effects may be cumulatively or synergisticallydisruptive to a target cell, particularly to cells disposed orpre-disposed to unregulated growth (i.e., cancerous cells). Othercytotoxic or disruptive effects of the energy application as describeherein may occur due, for example, to application of mild hyperthermia(e.g., mild heating of tissue between about 40 to 48 degrees C.; or lessthan about 50 degrees C.); ion disruption, disruption of membranestability, integrity or function; and the like.

Systems and probes of the present invention, as further described below,can include one or more expandable elements (e.g., balloon) that can beindividually positioned at a target location then deployed or “inflated”to achieve improved contact with surrounding tissues (e.g., urethralwall), maximum surface area and optimal distribution of the therapeuticfield. An electrically active segment of the expandable element willtypically include an electrically conductive material (e.g., silver,gold, etc.) coated or deposited, e.g., on a mylar balloon. In oneembodiment, prior to deployment and inflation, the expandable elementcan be contained inside a flexible catheter that can be guided to thetreatment area. Once the delivery catheter is positioned, the “balloon”can be deployed and expanded via the circulation of fluid through theballoon, which can have a selected or controlled temperature and may actas a heat sink. The therapeutic field can than be delivered via thesilver coating on the mylar balloon. Two or more probes deployed in thisfashion will serve to contain the field within the treatment area.

Electrodes and probes of the present invention can be coupled to controlsystem or control module designed to generate, deliver, monitor andcontrol the characteristics of the applied field within the specifiedtreatment parameters. In one embodiment, a control system includes apower source, an alternating current (AC) inverter, a signal generator,a signal amplifier, an oscilloscope, an operator interface and/ormonitor and a central processing unit (CPU). The control unit canmanually, automatically, or by computer programming or control, monitor,and/or display various processes and parameters of the energyapplication through electrodes and to the target tissue of the patient.While the control system and power source can include various possiblefrequency ranges, current frequency delivered to target tissue will beless than about 300 kHz, and typically about 50 kHz to about 250 kHz.Frequencies in this range have been observed as effective in preciselycontrolling the energy application to the target tissue, controllingthermal effects primarily to mild thermal application, andpreferentially destroying cancerous cells with limited or no observabledamage to non-cancerous tissues.

Energy application according to the present invention can furtherinclude mild or low levels of hyperthermia. In some embodiments, smallchanges/elevations in temperature in the target tissue region may occur,but will typically be no more than about 10 degrees C. above bodytemperature, and may be about 2 degrees to less than about 10 degrees C.above body temperature (e.g., normal human body temperature of about 38degrees C.). Thus, local tissue temperatures (e.g., average tissuetemperature in a volume of treated tissue) during treatment willtypically be less than about 50 degrees C., and typically within a rangeof about 40-48 degrees C. In one embodiment, average target tissuetemperature will be selected at about 42-45 degrees C. As target tissuetemperatures rise above about 40-42 degrees C. during treatment, thecytotoxic effects of energy delivery on cancerous cells of the targetregion are observably enhanced, possibly due to an additive and/orsynergistic effect of current field and hyperthermic effects. Where mildhyperthermic effects are substantially maintained below about 48 degreesC., the energy delivery according to the present invention appears tomore preferentially destroy cancerous cells compared to healthy ornon-cancerous cells of the target tissue region. Where energy deliveryinduces tissue heating substantially in excess of about 45-48 degrees C.(e.g., particularly above 48-50 degrees C.), the preferential cytotoxiceffects on cancerous cells may begin to diminish, with moreindiscriminate destruction of cancerous and non-cancerous cellsoccurring. Thus, a significant advantage of treatment methods accordingto the present invention includes the ability to precisely andaccurately control energy delivery and induced hyperthermic effects,such that tissue hyperthermia can be accurately controlled andmaintained in a desired temperature range(s)—e.g., temperature rangesselected for more targeted or preferential destruction of cancerouscells compared to non-cancerous cells.

Tissue temperatures can be selected or controlled in several ways. Inone embodiment, tissue temperatures can be controlled based on estimatedor known characteristics of the target tissue, such as tissue impedanceand tissue volume, blood flow or perfusion characteristics, and thelike, with energy application to the tissue selected to deliver anapproximated controlled mild increase in tissue temperature. In anotherembodiment, tissue temperature can be actively detected or monitored,e.g., by use of a feedback unit, during treatment, with temperaturemeasurements providing feedback control of energy delivery in order tomaintain a desired target tissue temperature or range. Temperaturecontrol measures can include electronics, programming, thermosensors andthe like, coupled with or included in a control unit or module of asystem of the invention. Further, use of inflatable/expandable balloonsand circulation heated/cooled inflation media further facilitatescontrol and delivery of the desired treatment temperature to the targettissue.

Energy application and induction of hyperthermia in a target tissueregion according to the present application can include delivery ofvarious types of energy delivery. As described, application of generallyintermediate frequency range (e.g., less than about 300 kHz) alternatingcurrent in the RF range has been observed as effective in establishingmild heating and hyperthermia, as well as current fields in a controlledmanner so as to provide a cytotoxic effect, and in some instances, apreferential destructive effect to cancerous cells of a target tissuevolume/region. It will be recognized, however, that additional energyapplications and/or ranges may be suitable for use according to thepresent invention, and that systems and methods of the present inventionmay be amenable to use with other or additional energy applications. Forexample, energy application can include current flow having frequenciesfound generally in the RF range, as well as microwave range, includinghigher frequencies such as 300-500 kHz and above, and may further beamenable to use with direct current applications. Applied current can bepulsed and/or continuously applied, and energy delivery can be coupledwith a feedback-type system (e.g., thermocouple positioned in the targettissue) to maintain energy application and/or tissue heating in adesired range. Methods of the present invention can include any one ormore (e.g., combination) of different energy applications, inducedtemperatures, etc. as described herein.

In certain embodiments, particularly where energy application isselected for lower power delivery/ablation, the control system can bedesigned to be battery powered and is typically isolated from ground. ACcurrent is derived from the integrated power inverter. An intermediatefrequency (e.g., less than 300 kHz; or about 50 kHz to about 250 kHz)alternating current, sinusoidal waveform signal is produced from thesignal generator. The signal is then amplified, in one non-limitingexample to a current range of 5 mA to 50 mA and voltage of up to 20 Vrmsper zone. Field characteristics including waveform, frequency, currentand voltage are monitored by an integrated oscilloscope. Scope readingsare displayed on the operator interface monitor. An integrated CPUmonitors overall system power consumption and availability and controlsthe output of the signal generator and amplifier based on the treatmentparameters input by the operator. The operator can define treatmentparameters to include maximum voltage, maximum current or temperature,maximum power, and the like. In another embodiment, the applied fieldcan be cycled on and off, e.g., at a high rate, to keep the temperaturerelatively constant and with the duty cycle (e.g., on time-off time)adjusted to accurately control temperature.

Imaging systems and devices can be included in the methods and systemsof the present invention. For example, the target tissue region can beidentified and/or characterized using conventional imaging methods suchas ultrasound, computed tomography (CT) scanning, X-ray imaging, nuclearimaging, magnetic resonance imaging (MRI), electromagnetic imaging, andthe like. In some embodiments, characteristics of the tumor, includingthose identified using imaging methods, can also be used in selectingablation parameters, such as energy application as well as the shapeand/or geometry of the electrodes. Additionally, these or other knownimaging systems can be used for positioning and placement of the devicesand/or electrodes in a patient's tissues.

As noted above, access to the target tissue or prostate tissue can begained through the urethra of the patient. Referring to FIG. 1, aurethral access system 10 according to the present invention isillustrated. The system includes an elongated probe 12 that can beinserted in the urethra (U) of a patient via the penis (P), and advancedalong the urethra (U) to the desired location within the patient's body,specifically at a target location in the prostate tissue or gland (P).The probe includes a flexible catheter having an elongated shaft 14 thatcan be bent or flexed while advanced into and through the urethra (U).The probe 12 includes a distal tip 16, that can be shaped (e.g.,rounded) to minimize damage or trauma to the urethral wall duringpositioning or use. The probe 12 can optionally include a drainage lumen(not shown) that allows fluid communication between an area distal tothe distal tip 16 and the exterior or a proximal portion of the probe,so as to allow draining or flushing of contents of the bladder (B)during treatment and use of the probe 12.

The urethral probe 12 includes a proximal end and a distal portionhaving an expandable member 18, such as a balloon configured forexpansion in the urethra (U) of the patient. The proximal end 20 ispositioned outside the patient's body during use, and can include a hubor handle that can be coupled to a controller or control unit 22 thatcan include a power source. The expandable member 18 includes conductiveelectrode elements patterned or disposed on an outer surface of theexpandable member 18. The probe 12 will include an elongated bodyextending from the proximal portion of the device to the distal portion,and the elongated body can include an inner lumen or passage withelectrical coupling members, such as insulated wires, for coupling theelectrode elements of the expandable member 18 to the proximal endand/or an externally positioned controller and/or power source 22.

The probe 12 will be designed to include electrode elements that can bepositioned in the desired location and used for delivery of electricfields to the target tissue for treatment according to the presentinvention. Various embodiments of electrode elements can be included inthe present invention and the probe 12 can be designed or configured fordelivery of electrical fields, for example, between the expandablemember 18 and opposing electrode(s) (e.g., secondary electrodes)positioned in or in the vicinity of the prostate tissue (P), withcurrent fields in some embodiments established between electrodes andtypically in a plurality of directions (e.g., radially) through a volumeof tissue. Electrode elements of the expandable member 18 can includeconductive material deposited or patterned on a surface or at least aportion of the expandable member 18 that is brought into contact withthe walls of the urethra (U) during treatment. In one embodiment, theexpandable member 18 can be configured in a deployable configuration,such that the expandable member 18 may be positioned within the probe 12shaft and then deployed from the probe 12 (e.g., from the distal end ortip of the probe) and expanded at the desired location. For example, theexpandable member 18 can be positioned or disposed within in the probe12 shaft or portion of the elongate body (e.g., shaft lumen) duringadvancement and positioning of the probe 12, and deployed from the probe12 once a desired position in the patient's urethra (U) has beenreached. Alternatively, in another embodiment, the expandable member 18or balloon (e.g., electrode patterned balloon) can be coupled andpositioned along the length of the probe 12 on an outer surface, withinflation or expansion of the expandable member 18 controlled by anexternal pressure source coupled to the proximal portion of the probe.

As indicated in FIG. 1, the urethra (U) of the patient will include alength (l) passing through the prostate tissue (P) until reaching thebladder (B). The expandable member 18 of the probe 12 can includevarious shapes and configurations selected to span any portion of thelength (l). The expandable member 18 can be configured to span theentire length (l) (or more) or may be sized to span less than the entireportion. The expandable member 18 may be positioned at any portion alongthe length (l) during treatment, as well as elsewhere along thepatient's urethra (U), including portions at or adjacent to locationswhere the urethra enters or exits the prostate tissue (P) area.

A probe 12 may include one or more electrodes (e.g., secondaryelectrodes) that can be positioned within the probe 12 and deployed fromthe probe 12 and into the prostate tissue (P). For example, suchsecondary electrodes can be positioned in the probe shaft 14 or bodyduring advancement and positioning of the probe 12, and deployed fromthe probe 12 once a desired position has been reached. Deployable probes12 can include needle-like electrodes, which can include a shape memorymetal and configured to assume a desired shape when deployed, e.g., asdiscussed further below.

During use, field delivery can occur with current flow between anelectrode elements of the urethral probe 12 and electrode(s) spaced fromthe urethral probe 12, such as electrodes positioned in the prostatetissue (P) or in the rectal area (R). As above, electrode elements,including electrodes of the expandable member 18, will be connected toan external power source or power unit (e.g., power source of controlsystem or unit) 22, which will include a means of generating electricalpower for operation of the system and probe 12, and application ofelectrical current to the target tissue as described herein. The powerunit can include or be operably coupled to additional components, suchas a control unit, driver unit, user interface, and the like (see, e.g.,infra).

System 10 further includes an imaging device 24, such as an ultrasonicimaging probe, for providing images of tissues for example duringpositioning and/or use of the probe 12. The device 24 includes a distalimaging portion 26 including electronics and imaging components (e.g.,ultrasonic scanning transducer), which can be inserted in the patient'srectum (R) and positioned against the rectal wall near the prostate (P).Imaging device 24 can include those commonly used for diagnosticmedicine, such as commercially available ultrasonic imaging devicesincluding devices similar to or as provided by Accuson, Inc. (MountainView, Calif.). The imaging portion 26 can scan a region of the tissue togenerate an image of the tissue, rectal wall (R), prostate (P), urethra(U), and/or the probe 12 located in the patient's urethra (U). Theimaging device 24 can be connected to an image processing unit 28 and adisplay unit 30, as is common practice. In use, the display 30 providesimages (e.g., real-time ultrasonic images) of the prostate (P) with theposition of the probe 12 relative to the prostate (P) and target area,the bladder (B), etc. to help guide or confirm positioning of the probe12 within the prostate (P) prior to delivery of treatment energy.

As discussed above, a probe 12 of a system, e.g., as illustrated in FIG.1, will include electrode element patterned or otherwise disposed on anexpandable member 18 or balloon disposed on a distal portion of theprobe. A probe 12 can include a catheter probe having a shaft and adistally positioned balloon member having electrode elements disposed(e.g., deposited, patterned, etc.) thereon. The balloon can be coupledto one or more fluid sources positioned externally, as well as apressure source and/or controller for inflation and deflation of theballoon. In one embodiment, the balloon can be configured such that afluid can be circulated through the balloon and may be utilized tofurther effect or control temperature of tissues proximate to theballoon. The probe 12 further includes a proximal hub 20 that caninclude one or more electrical connections for coupling the electrodeelements to an external power source and/or control unit 22, as well asfluid connections for fluidic access and control of balloon actuationand inflation, as well as circulation of fluid (e.g., cooling fluid)through the balloon. In an embodiment where the probe 12 furtherincludes one or more deployable electrodes, actuation and positioning ofsuch deployable electrodes can be controlled from the proximal end 20 ofthe probe 12, such as through the hub. In other embodiments, currentflow can extend between electrode elements of the expandable member 18positioned in the patient's urethra (U) and one or more electrodeelements (e.g., secondary electrodes) spaced from the positionedexpandable member 18, and may be separate from the urethral probe 12,and positioned on an opposing side of the urethral wall. For example,needle electrodes can be separately advanced through the perineum of thepatient and positioned within the prostate tissue (P) around the urethra(U), with energy delivery establishing current flow between electrodeelements of the urethral probe 12 and needle electrodes positioned inthe prostate tissue (P). In yet another embodiment, electrode elements(e.g., electrodes disposed on an expandable balloon 18) can bepositioned in the rectal cavity adjacent to the rectal wall (R), withcurrent flow established between electrode elements of the urethralprobe 12 and electrode elements of the rectally positioned device.Exemplary embodiments of system configurations and electrode positioningare discussed further below.

Referring to FIG. 2, a urethral probe 40 according to the presentinvention is described. The probe 40 includes a flexible elongate shaftor body 42, including a distal portion 44 and a proximal portion 46. Thedistal portion 44 includes an expandable balloon 48 or expandable memberhaving electrode elements 50, 52 disposed thereon. The electrodeelements 50, 52 may be electrically conductive and will include flexibleor expandable materials or configurations that can be expanded with theexpansion of the expandable member 48 and, when positioned in theurethra of a patient, electrode elements 50, 52 can be brought intoimproved contact with the urethral wall. The electrode elements 50, 52can be connected to an external power source 54 and control unit 56 forenergy delivery and establishing electric current fields between theelectrode elements 50, 52 of the expandable member 48 and one or moreelectrodes 58, 60 (e.g., secondary electrodes) spaced from theexpandable member 48. Secondary electrodes 58, 60 may be integrated orphysically connected to the probe 40 (e.g., deployable therefrom) or canbe separate and independently positionable, and may at least partiallydefine a separate electrode device (see, e.g., secondary electrodeembodiments discussed further below). Secondary electrodes 58, 60 may beelectrically connected to the power source 54 and control unit 56. Insome instances, current flow can be established between secondaryelectrodes 58, 60.

The distal expandable member 48 can be inflated with an inflation media(e.g., air, fluid, etc.) from an external source, and upon inflation,can provide improved contact of the electrode elements 50, 52 of theexpandable member 48 with the urethral wall. The distal expandablemember 48 can be connected with an external inflation source about aninflation hub positioned at the proximal portion 46 of the probe 40.Inflation media can be flowed into the expandable member 48 to obtain adesired pressure within the expandable member 48 for member expansion,and may be further circulated at a desired inflation pressure throughthe expansion member 48, as indicated by the directional arrows shown onthe expandable member 48 in FIG. 2. In one embodiment, the inflationmedia can be heated or cooled to a desired temperature, e.g., by heatingor cooling at an external location, and circulated through theexpandable member 48 to further control tissue temperature at thetreatment location, either by delivering additional heating or coolingenergy, and/or by acting as a sort of heat sink to maintain local tissuetemperature at a substantially constant or desired temperature range.

The probe 40 can further include an opening or port 62 at the distalportion 44 of the probe 40, with the port coupled 62 with a channel orlumen passing through the elongate shaft 42 and to the externallypositioned hub 64, and may provide fluid communication to a locationdistal to the probe (e.g., distal the distal tip of the probe 40), suchas drainage or infusion of fluids to a location distal to the probe 40(e.g., the patient's bladder). While the probe 40 is illustrated in FIG.2 as having a single expandable member 48, it will be understood thatthis and other designs/configurations of the probe 40 may optionallyfurther include one or more additional expandable members 48 orballoons. For example, the probe 40 may include a Foley-type catheterdesign, where the probe includes a second balloon located on the probe40 body distal to the expandable member 48 for positioning and/oranchoring in the patient's bladder during use of the probe or treatment(see, e.g., FIG. 9).

As described above, a urethral probe 40 of the present invention willinclude a distal portion 44 having an expandable member 48 including oneor more electrode elements 50, 52 that can be brought into contact withthe patient's urethral wall at a desired location. The electrodeelements 50, 52 may be electrically conductive, exposed electrodecoating, sheets, wires, films, braids, flexible materials, and the likethat can be expanded with the expansion of the expandable member 48 and,when positioned in the urethra of a patient, electrode elements 50, 52can be brought into improved contact with the urethral wall. Theelectrode elements 50, 52 may be patterned, disposed, or spaced on theexpandable member 48 in various configurations and designs to suitclinical or treatment needs. In one embodiment, electrode elements 50,52 can include a somewhat uniform coating that may partially or entirelycoat or cover the surface of an expandable member 48. FIG. 3Aillustrates a probe 70 having an expandable member 72 with an electrodelayer 74 that surrounding or covering a portion of expandable member 72,and forms a sort of annular ring substantially around the circumferenceof the expandable member 72 portion. The electrode layer 74 iselectrically coupled to a conductive cable 76 such as an insulated wirethat can pass along or through probe body or shaft 78 (e.g., internallumen) and couplable to an external power source as described above.FIG. 3B shows another embodiment of a urethral probe according to thepresent invention. The probe 80 includes a plurality of electrodeelements 82 disposed longitudinally along the surface of an expandablemember 84, with each electrode element 82 independently addressed byelectrical couples 86 (e.g., conductive cables, insulated wires, or thelike) passing along (e.g., embedded in the probe body) or through theprobe shaft 88 and out the proximal end. Various electrode patterns andconfigurations can be included in probe designs according to the presentinvention, and probes described herein will not be limited to anyparticular pattern or design.

Energy delivery between positioned electrodes is further described withreference to FIGS. 4A through 4C. As described above, the presentinvention can include insertion and positioning of a urethral probewithin a portion of the urethra passing through the patient's prostatetissue, and delivering a current field between electrode elements of aprobe's expandable member and secondary electrode(s) spaced from theurethra and expandable member, and, therefore, establishing the desiredcurrent through the target tissue disposed between opposing electrodes.Electrodes can be positioned and activated in pairs or groups such thatthe desired electric field is delivered to the target tissue between theelectrodes and, in some instances, in a radial orientation or in aplurality of different directions. FIG. 4A conceptually illustratesestablishment of a current field 92 with two spaced electrode elements(e₁ and e₂) as a basic field delivery unit 90 according to an embodimentof the present invention. As shown, distal portions of two electrodes(e₁ and e₂) of a plurality positioned in a target tissue 94 andactivated as an electrode pair or circuit, with the applied currentsubstantially contained between the two. Thus, electrodes can beactivated in a bipolar configuration, with current flowing betweenelectrodes (e.g., between e₁ and e₂) and the tissue 94 between theelectrodes acting as a flow medium or current pathway between theelectrodes. Positioning and activation of pairs or relatively smallgroups of electrodes in this manner allows more precise control of thecurrent applied to the tissue 94, containment of the applied field 92 tothe desired location, as well control of heating or limited temperatureincrease in the target tissue 94. Several factors may lend to improvedcontrol of therapeutic effects of the delivered fields according to thepresent invention. First, as discussed above activating electrode in abipolar configuration or so as to form a circuit allows the appliedfield to substantially be contained within the volume defined by thepositioned electrodes. Second, energy delivery can be selected (e.g.,frequency ranges between about 50 kHz to about 300 kHz) such that tissueheating occurs predominately due to tissue resistance, rather than thehigh levels of frictional heating observed at high frequencies (e.g.,500 kHz or greater). High frequency/high friction type heating istypically characterized by significant tissue temperature gradientsthroughout the treated tissue, with substantially higher tissuetemperatures occurring near the electrode. Where high friction typeheating is reduced relative to heating occurring due to tissueresistance, a more constant and controlled heating between opposingelectrodes can be delivered.

In some embodiments of therapeutic energy delivery according to thepresent invention, electrode positioning and/or device configurationadvantageously allows delivery of field throughout a target tissuevolume in a plurality of different directions, such as radial fieldorientation and application through the target volume. FIGS. 4B and 4Cillustrate simplified plan views of electrode positioning and spacingfor field application according to exemplary embodiments of the presentinvention. As shown in FIG. 4B, a simple four electrode grouping can beselected for use in treatment, with an applied field established andcurrent flowing between a centrally positioned electrode 102 and outeror secondary electrodes 104, 106, 108 positioned spaced from the centerelectrode 102. Thus, an exemplary delivery unit 100 can include acentrally located electrode 102 surrounded by spaced electrodes 104,106, 108, with the applied field extending between the central electrodeand the outer spaced electrodes. In this manner, the outer electrodes104, 106, 108 can essentially define an ablation volume with theinner/central electrode 102 positioned within the volume. Field deliveryin this way is advantageously controlled and substantially containedwithin the ablation volume. Furthermore, field delivery in this manneradvantageously allows a current field to be established with currentflow in a radial and plurality of different directions through thetreatment volume, e.g., extending through or from a flow center locatedabout the centrally positioned electrode 102. As will be recognized, thecentrally positioned electrode, such as electrode 102, can include anelectrode element of an expandable member of a urethral probe asdescribed above (see, e.g., FIG. 1-2), with outer or secondaryelectrodes 104, 106, 108 spaced from the urethral probe and positionedin the prostate tissue of the patient. FIG. 4C illustrates exemplaryelectrode positioning including outer electrodes 112, 114, 116, 118 andan inner or centrally located electrode 120, for defining a discretetarget tissue volume for treatment and establishing electric/treatmentfields (indicated by arrows) between the electrodes, which can include aplurality of different directions or extend radially through the volume.Electrode positioning will not be limited to any particularconfiguration, and various arrangements will be possible.

Another embodiment of the present invention is described with referenceto FIGS. 5A and 5B. In this embodiment, elongate needle electrodes 132,134 are inserted into or near the prostate tissue (P) for establishingcurrent field 136 between the positioned needle electrodes 132, 134 anda urethral probe 138 positioned in the patient's urethra (U). Atransurethral probe 138 as described above is advanced along thepatient's urethra (U) and positioned in the desired location. The probe138 includes a proximal portion 140 and a distal portion having anexpandable member 142 with electrode element(s) 144 disposed thereon.The electrode element 144 of the urethral probe 138 can be coupled,e.g., about the proximal end or hub 140, to a control unit and/or powersource 146. Elongate needle electrodes 132, 134 are advanced through thetissue of the patient, such as by insertion (e.g., percutaneous punctureand insertion) through the perineum of the patient and into the prostatetissue (P) or near the tissue (e.g., at the prostate tissue margin).Needle electrodes 132, 134 include a distal portion 148, 150 that willbe electrically active or configured for energy delivery according tothe present invention. Needle electrodes 132, 134 further include aproximal portion 152, 154 that can be positioned external the patient'sbody during use and manipulated for electrode positioning, and furtherelectrically coupled to the control unit/power source 146. Needleelectrodes 132, 134 may be at least partially insulated along a lengthso as to more precisely deliver energy or establish current at thedesired location. Needle electrodes 132, 134 may be positioned andmanipulated independently and/or with use of a template or guideapparatus, such as a template block having various spaced guide holes.Alternatively, two or more needles can be coupled with a housing or acartridge-type apparatus for guided advancement and positioning. Boththe urethral probe 138 and the needle electrodes 132, 134, like othercomponents or embodiments, can be inserted and positioned under theguidance of one or more various imaging devices such as ultrasound, CT,MRI, or X-rays, including those conventionally used to monitor andassist the positioning of probes, catheters, and the like during varioustypes of prostate treatments.

One advantage of the treatment approach as described above withreference to FIG. 5A is that needle electrodes 132, 134 can bepositioned at various locations and spacings, so as to permit a widevariety of treatment configurations. In one embodiment, as illustratedin FIG. 5B, needle electrodes 156, 158, 160 can be positioned in theprostate tissue (P) and around the area of the urethra (U) where theurethra probe 138 is positioned. FIG. 5B shows a cross-sectional view ofa urethra (U) with an expandable member 142 of a probe positionedtherein and electrodes 156, 158, 160 positioned in the prostate tissue(P) around the urethra (U). The positioned needle electrodes 156, 158,160, according to this embodiment, will substantially define thetreatment volume, and current field 162 can be established flowingbetween the inner placed urethral probe electrode elements and theneedle electrodes positioned 156, 158, 160 in the prostate tissue (P).Thus, current field 162 can be established flowing radially throughoutthe defined treatment volume around the urethra (U). The presentinvention is not limited to any particular electrode arrangement, andvarious electrode configurations and positionings can be utilized.

As described above, electrodes will include a substantially rigidelongate body and a distal portion having an electrically active regionfor delivering the desired current field to the target tissue. Fortissue piercing or percutaneous access and advancement, needleelectrodes will typically include a pointed or sharpened distal tip.Various electrode configurations and designs can be utilized and thecurrent invention is not limited to any particular electrode design.Electrodes, for example, can be differentially insulated such thatcurrent delivery occurs at a non-insulated or thinly insulated region ofthe electrode. FIG. 6A illustrates a straight needle electrode having anelectrically active region 172 and a region 174, which isnon-electrically active. The needle can include an electricallyconductive material (e.g., stainless steel, silver, gold, etc.) havingan insulating coating on region 174 and non-insulated on the activeregion 172. Electrodes can include a single active region or a pluralityof active regions, as shown in FIG. 6B having active regions 176, 178.In addition to more rigid straight needle type electrodes, electrodescan include a deployable element 180 that can be retractable andpositioned within a lumen of a catheter-type device, as shown in FIG.6C. The electrode element 180 can be curved (as shown) or can besubstantially straight or linear. Various needle/electrode sizes and/orconfigurations may be utilized, and can include, without limitation,needles ranging from about 15 to about 27 gauge in size.

In another aspect, systems and methods include an elongate urethralprobe, a distal expandable member with conductive electrode elements andone or more secondary electrodes deployable from a body of the elongateprobe. The secondary electrodes can include an electrically conductive,shape memory metal (e.g., Nitinol) and can be deployed from the body ofthe elongate probes and advanced to a position spaced from theexpandable member for current delivery between the deployable electrodesand the electrode elements of the expandable member. Deployableelectrodes will include a proximal portion and a distal portion, withthe distal portion being substantially disposed within the elongate bodyduring non-deployed phase. The electrodes can extend through the body ofthe elongate probe, with the proximal portion extending out the proximalend of the elongate probe. Electrodes can be controlled/actuated fromthe proximal end of the probe and deployed from or retracted into thedistal portion of the probe by application of force to the proximal endof the electrode.

A urethral probe 190 including an expandable member 192 and deployableelectrode 194, 196, according to one embodiment of the presentinvention, is described with reference to FIG. 7A. The probe 190includes a flexible elongate body 198 having a proximal portion and adistal portion. The distal portion includes an expandable member 192,similar to embodiments described elsewhere herein in having anexpandable member, such as a balloon, with electrode elements 194, 196disposed thereon. The body of the probe further includes a lumen withdeployable electrodes 194, 196 positioned therein. Deployment ofelectrodes 194, 196 can include application of a force to the proximalportion of an electrode 194, 196 so as to advance the distal portion ofthe electrode 194, 196 from the lumen of the elongate body 198 fordeployment and positioning of the electrode 194, 196. In certainembodiments, including the probe 190 illustrated in FIG. 7A, deployableelectrodes 194, 196 further can optionally include a positioningmicrocatheter 200. The microcatheter includes an inner lumen with thesmaller electrode 194 positioned therein and deployable from themicrocatheter 200. Deployment of the microcatheter 200 includesapplication of force to the proximal portion of the microcatheter 200and advancement of the distal portion of the microcatheter 200 from thelumen of the body for deployment and initial positioning or aiming.Deploying the microcatheter 200 from the lumen guides the microcatheter200 along a guide path or tissue penetration path through the urethraand into the prostate tissue and can further curve in an initial desireddirection or at an angle. Following deployment of the microcatheter 200,electrode 194 can be deployed from the microcatheter 200 for furtherpositioning of the electrode 194 as illustrated in FIG. 7A. In use, theelectrode 194 at least partially defines the outer portion or perimeterof the ablation volume, with the expandable member 192 positioned atabout the center of the volume (e.g., current flow center), permittingcurrent flow extending radially within the volume and between electrodes202 of the expandable member 192 and the deployed electrode 194. Whileuse of an aiming microcatheter 200 can advantageously facilitateimproved positioning of the deployed electrode 194, probe mayalternatively be designed such that electrodes deploy directly from theprobe body and in the absence of an aiming microcatheter 200.

Use of a urethral probe including deployable electrodes and a distalexpandable member having electrode elements, according to an embodimentof the present invention, is described with reference to FIGS. 7B and7C. As illustrated in FIG. 7B, a distal portion of a urethral probe 210is advanced through the patient's urethra (U) so as to position theexpandable member 212 at a target location in the patient's urethra (U).The positioned expandable member 212 is inflated or expanded at thetarget location so as to position the conductive electrode elements 214in better or improved contact with an inner surface of the patient'surethra (U) at the target location. As shown in FIG. 7C, the deployableelectrodes 216, 218 can be advanced or deployed from the body of theprobe 210 and through the urethral wall into the prostate tissue (P). Asdeployed, the secondary electrodes 216, 218 are spaced from theexpandable member 212 positioned in the urethra (U). The deployedelectrodes 216, 218 advanced or positioned in this manner can bepositioned to substantially define an ablation volume with theexpandable member 212 positioned within the ablation volume. Once theprobe 210 is positioned as desired, and electrodes 216, 218 deployed, anelectrical current flow can be established between the electrodeelements 214 of the expandable member 212 and the secondary electrodes216, 218.

In another aspect, a system of the present invention can include use ofa urethral probe positioned in the urethra of the patient and a probepositioned in the rectum of the patient, with current field establishedbetween conductive electrode elements of the urethral and rectal probes,and through the tissue disposed therebetween. In such an embodiment, aurethral probe can include an elongate flexible probe as describedabove, including a proximal end and a distal end having an expandablemember including electrode elements. The system further includes arectal probe having a distal portion with an expandable member similarto the expandable member of the urethral probe. The rectal probe willinclude one or more electrode elements disposed on a surface of anexpandable member. A control system including a power source is furtherincluded, the control system can be coupled to the elongate urethralprobe and rectal probe and configured to provide electrical current tothe electrodes so as to establish a current flow through a volume of thepatient's prostate tissue and between the electrode elements of theurethral probe and electrode elements of the rectal probe.

A system 230 for establishing current flow between a urethral probe 232and a rectal probe 234, according to the present invention is describedwith reference to FIGS. 8A and 8B. A urethral probe 232 is included andcan include a probe as described above (see, e.g., FIGS. 1-3). The probe232 includes a flexible elongate shaft or body, including a distalportion and a proximal portion. The distal portion includes anexpandable balloon or expandable member 236 having electrode elements238 disposed thereon, and can be expanded with the expansion of theexpandable member 236 with electrode elements 238 brought intobetter/improved contact with the urethral wall. Similar to the urethralprobe 232, the rectal probe 234 includes an elongate body with a distalportion including an expandable member 240, such as a balloon, havingelectrode elements 242 disposed on one or more surfaces. Whileconceptually similar in design, the rectal probe 234 can be sized andconfigured for positioning and use in a rectal cavity (R), rather thanin a urethral lumen (U). Further, electrode elements 242 on the rectalprobe expandable member 240 will typically be substantially confined orpositioned on a side or surfaces of the expandable member 240 facing theprostate wall during energy delivery. Thus, the expandable member 240 ofthe rectal probe 234 need not necessarily include electrode elementsspaced annularly around the expandable member 240 (though such aconfiguration may be utilized), but instead may include electrodeelements 242 disposed on a discrete region or surface(s). The rectalprobe 234, during use, is positioned in the patient's rectum (R) andupon expansion of the expandable member 240 the electrode elements 242of the expandable member 240 are brought into improved contact with aportion of the rectal wall proximate to the prostate tissue (P).

Both the rectal probe 234 and the urethral probe 232 can be connected toan external power source and control unit for energy delivery andestablishing electric current fields between the electrode elements ofthe urethral probe expandable member and electrode elements of therectal probe expandable member spaced from the expandable member.Current flow established between the expandable members 236 and 240 isindicated by current flow arrows. FIG. 8B illustrates a cross-sectionalview of a positioned urethral probe 232 and a positioned rectal probe234, with current flow (indicated by field arrows) established betweenthe expandable members 236 and 240 of the urethral probe 232 and rectalprobe 234, respectively. As shown, the system can further includeelectrodes 246 positioned in the prostate tissue, which can includeelectrodes deployable from the urethral probe 232 or positioned elongateneedle electrodes as described above.

Similar to described above, inflation media or fluid can be flowed intoor circulated through either the urethral probe expandable member 236 orthe rectal probe expandable member 240, or both. As above, fluid can beflowed at a selected temperature for heating or cooling of the tissuesof the treatment areas, and/or may facilitate maintenance of the tissuesat a desired treatment temperature.

As noted above, a urethral probe according to the present invention caninclude one or more positioning members, such as an expandable balloon,for applying a positioning force to secure positioning of the probe inthe desired location. For example, while urethral probes are illustratedabove as having a single expandable member, it will be understood thatthis and other designs/configurations of the probe may optionallyfurther include one or more additional expandable members or balloons.For example, as illustrated in FIG. 9, a urethral probe 250 of theinvention can include a Foley-type catheter design, where the probeincludes a second balloon 252 located on the probe body distal to theexpandable member 254 for positioning and/or anchoring in the patient'sbladder (B) during use of the probe or treatment. The proximalexpandable member 254 will include electrode elements 256 for energydeliver as described above.

Another embodiment of the present invention is described with referenceto FIGS. 10A through 10C. As illustrated, an elongate urethral probehaving a plurality of deployable electrodes that can be advanced throughthe urethral wall and into the prostate tissue in a desired arrangementfor energy delivery. An elongate urethral probe 260 can include aproximal end, a distal portion, and a plurality of electrodes 262, 264,266 deployable from the distal portion. A method can include advancingthe distal portion of the probe through the patient's urethra so as toposition the distal portion near a target location in the patient'surethra. Once the distal portion is at the desired location, a pluralityof outer or secondary electrodes 264, 266 can be deployed from thedistal portion of the probe, through the urethral wall, and into theprostate tissue. The deployed outer or secondary electrodes 264, 266 canbe positioned to substantially define an ablation volume in the prostatetissue. Further, an inner or central electrode 262 can be deployed fromthe distal portion of the probe 260 and through the urethral wall andinto the prostate tissue (P) such that the inner/central electrode 262is positioned within the ablation volume. Once the urethral probe 260and needle electrodes 262, 264, 266 are positioned, treatment includesestablishing an electrical current flow 268 between the inner electrode262 and the one or more outer/secondary electrodes. FIG. 10B illustratescurrent flow about a flow center, between an inner or central electrode262 and to an outer perimeter or volume 270 defined substantially byouter positioned electrodes.

Referring to FIG. 10D, an elongate urethral probe 271 can additionallyor alternatively include one or more electrodes 272 deployable fromlocations along the body of the probe proximal to the distal tip.Deployable electrodes can be actuated and/or controlled from theproximal end of the probe, similar to as described above. Deployment ofthe electrodes can include application of a force to the proximal endcausing the electrodes to advance out of the probe body and through theurethral wall (U), and into the prostate tissue. Probe positioning, asshown, can include extending of the electrodes through the urethral wallin a direction perpendicular to the long axis of the probe body and intothe prostate tissue. Energy application can include activation ofelectrodes in pairs or groups, such as differential activation in pairsto establish current flow between activated pairs, as indicated by thefield arrow shown in FIG. 10D.

As mentioned above, various components of the systems described herein,including the urethral probe, rectal probe, the needle electrodes, andother components or embodiments, can be inserted and positioned underthe guidance of one or more various imaging devices such as ultrasound,CT, MRI, or X-rays, including those conventionally used to monitor andassist the positioning of probes, catheters, and the like during varioustypes of prostate treatments. Thus, probes and electrodes describedherein, for example, may include in part radiopaque or radiopaquemarkings (e.g., tip markings) such that their positioning can bevisualizable in X-ray, CT, MR or other types of imaging.

FIG. 11 shows a block diagram illustrating a system according to anembodiment of the present invention. The system 300 can includeincorporated therewith any device of the present invention for deliveryof energy to the patient, and includes a power unit 310 that deliversenergy to a driver unit 320 and than to electrode(s) of an inventivedevice. The components of the system individually or collectively, or ina combination of components, can comprise an energy source for a systemof the invention. A power unit 310 can include any means of generatingelectrical power used for operating a device of the invention andapplying electrical current to a target tissue as described herein. Apower unit 310 can include, for example, one or more electricalgenerators, batteries (e.g., portable battery unit), and the like. Thus,in one embodiment, a system of the invention can include a portableand/or battery operated device. A feedback unit 330 measures electricfield delivery parameters and/or characteristics of the tissue of thetarget tissue region, measured parameters/characteristics includingwithout limitation current, voltage, impedance, temperature, pH and thelike. One or more sensors (e.g., temperature sensor, impedance sensor,thermocouple, etc.) can be included in the system and can be coupledwith the device or system and/or separately positioned at or within thepatient's tissue. These sensors and/or the feedback unit 330 can be usedto monitor or control the delivery of energy to the tissue. The powerunit 310 and/or other components of the system can be driven by acontrol unit 340, which may be coupled with a user interface 350 forinput and/or control, for example, from a technician or physician. Thecontrol unit 340 and system 300 can be coupled with an imaging system360 (see above) for locating and/or characterizing the target tissueregion and/or location or positioning the device during use.

A control unit can include a, e.g., a computer or a wide variety ofproprietary or commercially available computers or systems having one ormore processing structures, a personal computer, and the like, with suchsystems often comprising data processing hardware and/or softwareconfigured to implement any one (or combination of) the method stepsdescribed herein. Any software will typically include machine readablecode of programming instructions embodied in a tangible media such as amemory, a digital or optical recovering media, optical, electrical, orwireless telemetry signals, or the like, and one or more of thesestructures may also be used to transmit data and information betweencomponents of the system in any wide variety of distributed orcentralized signal processing architectures.

Components of the system, including the controller, can be used tocontrol the amount of power or electrical energy delivered to the targettissue. Energy may be delivered in a programmed or pre-determined amountor may begin as an initial setting with modifications to the electricfield being made during the energy delivery and ablation process. In oneembodiment, for example, the system can deliver energy in a “scanningmode”, where electric field parameters, such as applied voltage andfrequency, include delivery across a predetermined range. Feedbackmechanisms can be used to monitor the electric field delivery inscanning mode and select from the delivery range parameters optimal forablation of the tissue being targeted.

Systems and devices of the present invention can, though notnecessarily, be used in conjunction with other systems, ablationsystems, cancer treatment systems, such as drug delivery, local orsystemic delivery, surgery, radiology or nuclear medicine systems (e.g.,radiation therapy), and the like. Another advantage of the presentinvention, is that treatment does not preclude follow-up treatment withother approaches, including conventional approaches such as surgery andradiation therapy. In some cases, treatment according to the presentinvention can occur in conjunction or combination with therapies such aschemotherapy. Similarly, devices can be modified to incorporatecomponents and/or aspects of other systems, such as drug deliverysystems, including drug delivery needles, electrodes, etc.

It is understood that the examples and embodiments described herein arefor illustrative purposes only and that various modifications or changesin light thereof will be suggested to persons skilled in the art and areto be included within the spirit and purview of this application andscope of the appended claims. Numerous different combinations arepossible, and such combinations are considered part of the presentinvention.

While preferred embodiments of the present invention have been shown anddescribed herein, it will be obvious to those skilled in the art thatsuch embodiments are provided by way of example only. Numerousvariations, changes, and substitutions will now occur to those skilledin the art without departing from the invention. It should be understoodthat various alternatives to the embodiments of the invention describedherein may be employed in practicing the invention. It is intended thatthe following claims define the scope of the invention and that methodsand structures within the scope of these claims and their equivalents becovered thereby.

What is claimed is:
 1. A system for preferential destruction of cancerous or hyperplastic cells of a prostate tissue of a patient, comprising: an elongate urethral probe comprising a proximal end and a distal portion having an expandable member, the expandable member comprising one or more conductive electrode elements; a rectal probe comprising one or more electrode elements disposed on a surface of an expandable member; and a control system comprising a power source, the control system coupled to the elongate urethral probe and rectal probe and configured to provide electrical current to the electrodes so as to establish a current flow through a volume of the patient's prostate tissue and between the electrode elements of the urethral probe and electrode elements of the rectal probe.
 2. The system of claim 1, wherein the system is configured to maintain an average target tissue temperature of less than about 50 degrees C.
 3. The system of claim 1, wherein the system is configured to maintain an average target tissue temperature of 45 degrees C. to 49 degrees C.
 4. The system of claim 1, wherein the electrical current comprises an alternating electrical current flow comprising a frequency of less than about 300 kHz.
 5. The system of claim 1, wherein the alternating electrical current flow comprising a frequency from about 50 kHz to about 300 kHz.
 6. The system of claim 1, wherein the alternating electrical current flow comprising a frequency of about 100 kHz.
 7. The system of claim 1, wherein system is configured to preferentially destroy cancerous cells of the prostate tissue in the volume relative to non-cancerous cells in the volume.
 8. The system of claim 1, wherein the control system is configured to cause delivery of electrical current from at least one of (a) at least one of the one or more conductive electrode elements of the urethral probe, or (b) at least one of the one or more electrode elements of the rectal probe.
 9. The system of claim 1, wherein the elongated urethral probe comprises one or more secondary electrodes deployable from a body of the elongated urethral probe.
 10. The system of claim 9, wherein the control system is configured to cause an alternating electrical current flow between the deployed one or more secondary electrodes and the electrode elements of the urethral probe.
 11. The system of claim 10, wherein the control system is configured to cause delivery of alternating electrical current from at least one of (a) at least one of the one or more conductive electrode elements of the urethral probe, (b) at least one of the one or more electrode elements of the rectal probe, or (c) at least one of one or more current transfer regions of the one or more secondary electrodes disposed within or adjacent to the prostate tissue and spaced from the electrode elements of the elongated urethral probe.
 12. A system for preferential destruction of cancerous or proliferating cells of a target tissue or of a body lumen passing through a target tissue of a patient, comprising: an elongate probe comprising a proximal end and a distal portion having an expandable member, the expandable member comprising one or more conductive electrode elements, the distal portion positionable in a body lumen of the patient; one or more secondary electrodes positionable within or adjacent to the target tissue and spaced from the electrode elements of the expandable member; and a control system comprising a power source, the control system coupled to the elongate probe and secondary electrode(s) and configured to provide electrical current to the probe and electrode(s) so as to establish a current flow through a volume of the patient's target tissue and between the electrode elements of the probe positioned in the body lumen of the patient and the positioned secondary electrode(s).
 13. The system of claim 12, wherein the system is configured to maintain an average target tissue temperature of less than about 50 degrees C. and the electrical current comprises an alternating electrical current flow comprising a frequency of from about 50 kHz to about 300 kHz.
 14. The system of claim 12, wherein at least one of the one or more secondary electrodes is deployable from a body of the elongated probe.
 15. The system of claim 12, wherein at least one of the one or more secondary electrodes is deployable from the distal portion of the elongated probe.
 16. The system of claim 12, wherein the secondary electrodes comprise elongated needle electrodes.
 17. The system of claim 12, wherein the control system is configured to cause delivery of alternating electrical current from at least one of (a) at least one of the one or more conductive electrode elements of the elongate probe, or (b) at least one of one or more current transfer regions of the one or more secondary electrodes that is disposed within or adjacent to the target tissue and spaced from the conductive electrode elements of the expandable member.
 18. The system of claim 12, further comprising a source for flowing a heated or cooled inflation media through the expandable member during energy delivery.
 19. The system of claim 12, further comprising a feedback unit configured to measure electric field delivery parameters and/or characteristics of the target tissue.
 20. The system of claim 12, further comprising an imaging device for providing images of tissues during use of the elongate probe. 